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141 Cards in this Set
- Front
- Back
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Orthomyxoviridae virus envelope
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Classical mucous viruses
Causes ORdinary flu Hemagglutinin (H protein) on the viral surface where RBCs attach and hide the virus from immune response. H protein attaches to sialic acid found in upper respiratory tract membranes so H protein is very important for attachment during infection. Neuraminidase (N protein) that helps the virus get into the cell. N protein cleaves neuraminic acid in mucin so it opens up the area for H protein to attach to sialic acid. It is also important in allowing the virus to get out of the cell by causing the final cleavage of sialic acid needed for it's escape during budding. People produce antibodies to these and this is how you get the H1N1 type of designation |
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Paramyxoviridae virus envelope
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F protein acts like glue to fuse uninfected cells together to evade the immune system
HN protein serves function for both H and N proteins (immune evasion and internalization) All Paramyxoviridae viruses adsorb and replicate in the upper respiratory tract, and often target kids. Measles and Mumps can then spread to other areas of the body once they have replicated (viremia) |
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HIV virus envelope
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Glycoprotein gp120 binds to receptors on monocytes, CD4+ cells, and microglia in the CNS
gp41 is only protein that is conserved in everyone so this is what is measured during HIV screening |
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All DNA viruses have ds DNA except:
All RNA viruses have ss DNA except: |
Parvoviridae is ss DNA
Reoviridae is ds RNA |
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All DNA viruses have linear nucleic acid except:
ALL DNA viruses lack an evelope except: |
Papovaviridae and Hepdnaviridae have circular DNA (can cause tumors and resistant to breakdown)
Herptoviridae, Poxviridae, and Hepdnaviridae have an envelope |
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Ways to deactivate viruses
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autoclave at 100 C for 30 minutes
Strong chlorine solutions (chlorox), formalin Anionic detergents (destroys envelopes and capsids to stop infectivity) Electromagnetic radiation Viruses that have envelopes are deactivated by detergents (soap, ether, etc.) |
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HIV modulation of immune system
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increased CCR5 serves to enhance HIV infection of monocytes & microglial cells
Secretion of "virokines" that mimic proteins in the immune system Hypersecretion of IL-10 shuts down the inflammatory response and antigen processing |
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Viruses can affect cells in 4 different ways
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1.) Cytocidal - results in cell death (characterized by presence of inclusion bodies)
2.) Steady-state - noncytocidal, but can cause damage in immunocompromised 3.) Hyperplasia - increased replication (HPV) 4.) Transformation - cell growth characteristics permanently altered (EBV and Burkitt's lymphoma) |
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Type of inclusion bodies for different viruses
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Cowdry type A intranuclear bodies - Characteristic of herpes viruses (found in nerve cells or epithelial cells)
Negri bodies - Rabies virus (in nerve cells) Guarnieri bodies - smallpox / vaccinia virus (inclusion body w/ "halo") |
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Steps in Viral Replication
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1.) Attachment via electrostatic bonding(most susceptible to prevention of infection, pH dependent, temperature independent)
2.) Penetration (receptor mediated endocytosis AKA viropexis, temperature dependent (girl needs to be hot to allow penetration), hijacks cytoskeleton to get where it needs to) 3.) Uncoating 4.) Early transcription (ALL VIRUSES USE DNA-DEPENDENT RNA POLYMERASE for this) 5.) Early translation (NON-STRUCTURAL, but shuts down cell synthesis, always in the cytoplasm) 6.) Genome replication 7.) Late transcription 8.) Late translation (first time you see something wrong in the cell, production of STRUCTURAL proteins) 9.) Assembly (factories within cell) 10.) Release (via cell lysis, budding, or through the ER / Golgi) |
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All DNA viruses replicate in nucleus except:
All RNA viruses replicate in cytoplasm except: |
Poxviridae is DNA virus that replicates in cytoplasm (Virus-associated DNA-dependent RNA polymerase)
Orthomixoviridae (virion-associated RNA-dependent RNA polymerase) & Retroviridae (virion-associated RNA-dependent DNA polymerase) are RNA viruses that replicate in nucleus |
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Cell attachment sites for HIV, Poliovirus, Orthomyxoviruses, Rabies virus, and Epstein-Barr virus
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1.) HIV attaches to CD4 receptors on helper T cells, macrophages, and microglial cells (CCR5 and CXCR4 are also involved)
2.) Polioviruses attach to poliovirus receptor PVI that is similar to ICAM 3.) Orthomyxoviruses and Paramyxoviruses attach to mucoprotein receptors in resp. tract 4.) Rabies virus attaches to nicotinic acetylcholine receptors 5.) Epstein-Barr virus attaches to C3d receptor on B lymphocytes |
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RNA virus strategy for 5' capping outside of the nucleus
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1.) Poliovirus mRNAs are not capped at all and translated by a cap-independent mechanism
2.) Influenza utilize 5' caps cleaved from host mRNAs |
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RNA virus strategy for polyadenylation
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1.) Reo and arenaviruses don't have polyA tails and rely on 3' stem-loop structures to protect 3' end
2.) Poliovirus use template-encoded 3' polyA tracts 3.) Influenza uses "stuttering" where RNA polymerase adds several hundred As by continuously copying the same short stretch of Us in the (-) sense strand |
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Constitutive transport elements
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cis elements that cause unspliced RNA to efficiently be transported from the nucleus to the cytoplasm for translation by host machinery
Used by simple retroviruses |
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Rev / Tat HIV system of transport
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HIV becomes active after latent period
Spliced proteins are made and produce Rev and Tat Tat promotes transcription, making even more Rev and Tat Rev continuously transports proteins out of the nucleus Eventually Rev starts to transport proteins out before they can be spliced. Since they are no longer spliced production of Rev and Tat cease Now have ample unspliced RNAs for mRNAs and Gag proteins |
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Translation strategies used by viruses
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1.) Polyproteins - One large polyprotein is expressed and then cleaved into several smaller peptides (difficult to regulate amount of different peptides)
2.) Leaky scanning - Weak start codons are utilized to get translation some of the time. Progressively stronger start codons are translated more often 3.) Reinitiation - Ribosome fails to fall off when it reaches stop codon because it often overlaps a start codon so it starts again (Influenza) 4.) Suppression - Gag stop codon is misread so translation continues and is later cleaved by proteases 5.) Frame shifting - Gag and pol encoded by overlaping reading frames. Before translation reaches gag stop codon, a frame shift within gag results in translation of truncated Gag fused to Pol 6.) Internal Ribosome Entry - Polio virus has a protease that cleaves initiation factor eIF4G, which stops cap-dependent translation. This cleavage product has a special IRES sequence that 40S ribosome binds to, joined by 60s and starts translation (Allows Polio to not need cap, and gives it the ability to start at an INTERNAL AUG) |
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Nuclear Localization Signals (NLS)
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Helps to get viral proteins to the nucleus so they can be assembled into viral particles
Viral proteins that don't have NLS can piggy-back on others that do Ensures that only components that are properly folded get to the nucleus |
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Genome transport to the cytoplasm for particle assembly by Influenza
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Retroviral genomes are produced in the nucleus and must be exported to the cytoplasm, and then localized to the inner side of the plasma membrane for particle assembly.
M1 forms a complex w/ genome, then NS2 binds to the complex and M1 protein targets the complex to the plasma membrane |
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Types of viral particle assembly
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1.) Concerted assembly - viral particles assembled in conjunction w/ nucleic acid (influenza)
2.) Sequential assembly - empty capsids are built and then nucleic acid is transported into capsids (Herpes virus) (As Herpes DNA goes into the capsid, scaffold proteins come out. When the right amount of DNA is in, "terminase" cleaves the DNA and the particle is assembled) 3.) Scaffold proteins - Adeno and Herpes virus require scaffold proteins to organize structures into completed capsids (scaffold proteins removed during DNA packaging) 4.) Self-assembly - mixing appropriate proteins together in vitro can result in self-assembly of capsids (Important in HPV vaccine) |
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Tegument (matrix) proteins
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Proteins b/w capsid and envelope that have immediate effect when they enter (can shut off host protein synth, etc.)
Found in Herpes viruses |
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Strategies for acquiring envelopes
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Most get their envelope by "budding" from cell membranes
1.) In Herpes viruses acquire their final envelope by budding into Golgi vesicles and then fusing with cell membrane 2.) Poxviruses evnelopment involves wrapping of Golgi vesicles around the virion and then they shed off one layer when they fuse w/ cell membrane |
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Strategies for acquiring envelopes
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1.) In Herpes viruses acquire their final envelope by budding into Golgi vesicles and then fusing with cell membrane
2.) Poxviruses evnelopment involves wrapping of Golgi vesicles around the virion and then they shed off one layer when they fuse w/ cell membrane |
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CD8+ T cells
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Direct damage via perforin pores and indirect damage via Cytokine Storm
Cause the damage seen in LCM Virus and Hepatitis viruses |
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CD4+, Th1, and Th2
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CD4+ are pro-inflammatory
Th1 cells are proinflammatory and recruit neutrophils Th2 is pro-antibody (anti-inflammatory) Viruses mess with the concentrations of each of these Live vaccine - Th1 response mediated Attenuated vaccine - Th2 response - Many children died when given attenuated Respiratory Synctivial Virus vaccine b/c ramped up Th2 response made them more susceptible |
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Viral strategies to inhibit Th cell Immune response
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1.) Block IFN-gamma, which decreases MHC Class II expression
2.) Redirects newly synthesized class II from ER to cytosol, where it is degraded 3.) Induce secretion of IL-10 to block inflammatory response and increase the pH of endosomes to block processing of antigens |
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Viral strategies to inhibit CTL cell immune response (CD8+)
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1.) Repress Class I heavy chain promoter
2.) Prevent IFN-gamma activation of Class I 3.) Block TAP - prevents peptides released by proteosome from being transported to the lumen of the ER, Class I is retained in the ER and degraded 4.) Proteins that misdirect Class I transport in the ER 5.) Protein that causes miss-folding of Class I so it is retained in the ER (Adenovirus) 6.) Proteins that bind to Class I and promote their endocytosis to cytoplasmic lysosomes 7.) HIV Nef protein binds to and retains class I in the ER / promotes endocytosis of Class I from the cell surface 8.) Ebola Virus proteins are resistant to cleavage by proteasomes so EBV peptides are not made and therefore cannot be presented |
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Source of Th peptides and CTL peptides
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Antigen Presenting Cells express EXOGENOUS peptides (peptides from antigens that they have endocytosed) (MHC Class II)
CTLs express ENDOGENOUS peptides derived from cytoplasmic proteins (MHC Class I) |
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Viral strategies to evade humoral (B Cell) immune response
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1.) Antigenic drift - alter the nature of the viral antigens by point mutations of relevant epitopes
2.) Antigenic shift - frequently and abruptly changing the antigenic composition of the virus by reassortment of genomic RNA (Influenza change their 8 independent RNA segments) Antigenic shift is more profound and can lead to genetic combinations of multiple strains forming a new strain |
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Viral strategies to evade innate immunity
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1.) Viruses can encode Class I homologs so that NK cells don't kill them
Infected cells release IFN, which upregulates Pkr and RNase L Pkr is a kinase that block viral protein production RNase L binds 2',5'-Oligo(A) made by dsRNA and activates RNase L to non-specifically degrade all mRNAs 2.) Virus secretes IFN-binding proteins 3.) Influenza proteins bind to and sequester dsRNA so they can't activate Pkr and RNAse L 4.) Herpes makes complex 2',5'-oligoadenylates that don't activate RNAse L 5.) Adenovirus binds Pkr and prevents its activation 6.) Block JAK/STAT pathway needed for IFN activation |
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Antibody test for acute viral hepatitis
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measure IgM
Diagnostic spike of IgM in acute infection |
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Hepatitis A
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Picornavirus
No Cirrhosis, not deadly Fecal/oral transmission Abrupt onset No carrier state or chronic liver disease Viremia precedes and continues through acute phase Identification of IgM anti-HAV is the diagnostic marker for acute Hepatitis A Past infection is determined by detection of HAV-IgG (convalescent phase antibody) Vaccine available Immune serum globulin given to infected individual's household |
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Hepatitis B
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The only Hepatitis causing virus that is a DNA virus (ds circular DNA)
Hepatitis B = Big (large virion) and Bad Dane particle associated w/ Hep B Chronic carrier state / chronic hepatitis Prolonged Viremia (unlike Hep A where it is hard to find it in blood) Can cause Fulminant hepatitis (Severe acute hepatitis w/ rapid liver destruction) or Hepatocellular carcinoma Parentral / sexual / perinatal transmission Older individuals have higher likelihood of having symptoms partially ds w/ 2 single stranded regions S region - codes for Hepatitis B surface antigen (HBsAg)(antibodies against this are protective) P region - codes for viral polymerase C region - codes for core protein (HBcAg) (antibodies against this are not protective) One of few non-retroviral viruses w/ revers transcription E antigen + = very infectious E antibody - = not infectious HBsAg only tells you infection present, but don't know if acute or chronic IgM anti-HBc is true marker of acute infection If patient makes anti-HBs = acute Patient doesn't make anti-HBs = disease goes chronic. HBsAg is always seen in chronic infection. Anti-HBs not there to make it drop off like in acute infection. HbeAg = high infectivity. Anti-HbeAg = low infectivity Vaccine available "Core Window" - HbsAG has fallen back down (-), Anti-HBs hasn't started yet (-), and anti-HBc (+) b/c there throughout the infection |
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Hepatitis B life cycle
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1.) Attachment
2.) Penetration into cytoplasm 3.) Uncoating - DNA transfered to cell nucleus by chaperones 4.) Partially double stranded viral DNA is then made full double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as template for 4 viral mRNAs 5.) Largest mRNA used to make new copies of genome, the CAPSID, and the viral DNA POLYMERASE 6.) Assembly - 4 transcripts go on to form progeny virions 7.) Release - long mRNA is transported back to cytoplasm where P protein synthesizes DNA via its revers transcriptase activity |
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Primary hepatocellular carcinoma
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Associated w/ chronic Hep B in areas where concomitant chronic immunosuppression such as malaria
100% fatal |
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Hepatitis C
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Flavivirus
Most Common Cause of chronic hepatitis and liver transplant in the US Often asymptomatic, but frequently goes chronic Parenteral transmission (transfusions) HCV RNA is the marker for infectivity anti-HCV indicates immunity only if no HCV persists since you can have elevated anti-HCV in the chronic phase as well Spike in ALT that resolves = acute infection Spike in ALT that begins to drop, but then get multimodal ALT elevations = distinct for chronic infection |
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Hepatitis D
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Even worse than Hep C
Can only get Hep D w/ Hep B already present or via co-infection w/ Hep B (Danger of diagnosing acute Hep B and missing Hep D) (Must steal Hep B envelope) Often leads to fulminant hepatitis (nitrogen in brain w/ bad prognosis) / chronic hepatitis / cirrhosis / coma Co-infection - HBV and HDV transmitted together such as IV drug use Superinfection - Person that already had Hep B gets Hep D. This can lead to a severe disease w/ higher rate of fulminant hepatitis unique circular RNA domain Look for Anti-HDV - decreases during HBV-HDV Co-infection, remains elevated during HBV-HDV Superinfection HDV RNA and HBsAg also remain during HBV-HDV Superinfection If you're monitoring a known Hep B patient and then get a new ALT spike, look for Hep D Prevention by Hep B via vaccination can help prevent against Hep D |
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Hepatitis E
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Low mortality except in pregnent women
Primarily fecal / oral transmission like Hep A Also like A, can't cause chronic hepatitis Virus in stool seen in pre-acute phase and persists through acute phase Spike in IgM anti-HEV seen in acute phase IgG anti-HEV mean immunity has developed |
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Picornaviridae characteristics
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RNA viruses
Icosahedral symmetry No envelope, ether resistant 4 adenosine base terminal protein hooked to RNA to make virus infectious Small amount of RNA makes many proteins from differential cleavage Enterovirus, Rhinovirus |
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Rhinovirus
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Cuse common cold and occasional respiratory disease
Killed by detergents and acidic stomach pH Infect nasal epithelium by secreting fluid for attachment Mild respiratory infection, but NO fever Many antigenic sites |
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Polioviruses
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Infection of anterior horn motor neurons results in flaccid paralysis leading to atrophy of a limb
Sensory neurons unaffected Vaccine can prevent Clinical disease, but virus still in humans Lesions spare the pons or the inferior olivary nuclei. Attack precentral guyrus and cerebellum Fecal/oral transmission Spreads from mouth and GI to tonsils and Peyer's patches - to deep cervical nodes (lymphatic phase) - into blood (viremic phase and usually ends here) - In very few patients virus can then spread to CNS (neurological phase) Usually polio is sublinical infection Unlike related Coxsackie and Echo viruses, Polio is rarely recovered from CSF Salk vaccine - inactivated, killed virus vaccine. Need booster injections, doesn't prevent growth in gut Sabin vaccine - live attenuated vaccine, prevents growth in gut, but can cause vaccine-associated paralytic poliomyelitis |
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Post Polio Syndrome
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disease that appears 30-40 years after acute polio infection
Fatigue, muscle pain, joint pain, cold intolerance Some motor neurons w/ polio die. The motor neurons that recover develop new terminal axon sprouts that reinnervate many more muscle cells. After many years, these motor neurons begin to break down causing new muscle weakness. |
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Coxsackieviruses
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Group A coxsackieviruses
1.)cause extensive myositis & flaccid paralysis (Polio is not the only cause) 2.) Can cause lymphonodular pharyngitis 3.) Hand foot and mouth disease Group B coxsackieviruses 1.) cause focal muscle lesions, fat pad necrosis and attack liver, heart (goes for fatty tissue) (paricarditis) 2.) Can cause meningitis |
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Echoviruses
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Found in alimentary tract
Similar to polioviruses and Coxsackieviruses (all Enteroviruses) Cause maculopapular rash, aseptic meningitis, encephalitis Similar to polioviruses and Coxackieviruses |
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Influenza Virus characteristics
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Orthomyxovirus properties
1.)Enveloped 2.)Segmented, singled stranded 3.)RNA (leads to rearrangements) A, B, and C types - A and B can cause epidemics Influenza B DOES NOT occur in subtypes. Influenza A does Host response dependent on recognition of envelope glycoproteins H glycoprotein spike - binds to cell surface to initiate viral entry (low pH of endosome induces conformational change) N glycoprotein spike - receptor destroying enzyme that cleaves sialic acid on the cell surface, which decreases the ability of virus to bind and causes release of newly budded progeny Doctors often worried about secondary infections so give antibiotics |
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Influenza A & B viruses
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Antigenic shift and antigenic drift (B only has antigenic drift)
transmission via inhalation of aerosolized droplets Runny nose is unusual, makes it distinct from common cold Complications more common in young and elderly (secondary infections, pneumonia) Clara cells located in the respiratory tract must cleave virus HA in order to have fusion to the membrane (gives tropism to resp. tract) Virus isolation in culture from nasopharyngeal wash is the gold standard for diagnosis Can also use RT-PCR, which is more rapid |
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Neuraminidase inhibitors
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prevent release of newly synthesized virus from the infected cell by inhibiting N glycoprotein.
No resistance |
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M2 Ion channel inhibitors
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Prevents H ion passage into cell to allow uncoating of virus
effective for Influenza A only Resistance can develop |
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Parainfluenza virus
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Paramyxoviridae virus
Enveloped w/ ssRNA genome Pleiomorphic structure Transmission by respiratory secretions Can cause Croup - infection of larynx and Upper Respiratory system that can cause swelling and airway narrowing. Stridor and barking cough is found. No vaccine & no antiviral drugs |
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Respiratory Syncytial virus
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MOST COMMON CAUSE of Bronchiolitis and pneumonia in infants.
The Leading cause of infant hospitalization in the U.S. Paramyxoviridae family Enveloped, pleiomorphic, ssRNA No variation to worry about (non segmented RNA and only 2 subgroups) G glycoprotein for attachment and F glycoprotein for fusion (*No H & N make it unique) cause acute upper respiratory infection (common in Pediatrics) Treatment is supportive including hydration and respiratory support Ribavirin - in vitro activity against RSV Palivisumab - antibody for prevention of RSV in infants w/ chronic lung disease |
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Common Cold Viruses
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Upper respiratory disease
Nasal stuffiness (not typical of influenza), sneezing, coryza, minimal or NO fever Most caused by rhinoviruses and coronaviruses w/ serotypes OC43 or 229E All are (+) RNA viruses Handwashing is primary method of prevention b/c need direct contact for transmission |
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Human Metapneumovirus
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Paramyxovirus family
enveloped ss negative-sense RNA virus Humans are only source of infection via contamination w/ respiratory secretions Outbreaks in winter and early spring (overlaps w/ RSV so hard to distinguish) Acute respiratory tract illness and one of MCC of bronchiolitis in infants No antivirals - treatment is supportive |
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Measles (Rubeola)
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Highly infectious via upper respiratory tract droplets
Fever w/ erythematous maculo-papular rash (starts on forehead and spreads down) Multiplies locally and then spreads via blood Humans are only host Order of pathogenesis has 3 phases: 1.) Prodrome - conjunctivitis, photophobia, cough, malaise 2.) Koplik's spots -spots in mouth w/ blue,white centers 3.) Rash Symptoms include "three C's" - Cough, coryza (runny nose), and conjunctivitis Koplick spots - whitish spots on buccal mucosa Ottitis media is most common complication. Also Laryngotracheitis Vitamin A recommended for infected children Ribavirin may work Isolate patients until 5 days after rash to prevent transmission Immunoglobulin available Active immunization w/ live vaccine recommended except in immunocompromised |
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Mumps
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"I have Bumps caused by Mumps"
Sweling of one or more of the salivary glands (usually parotid) enveloped ssRNA virus (Rubulavirus) Humans are only known host and spread through resp. secretions Most common in children 5-15, but worst disease in adults Can cause meningitis Causes Orchitis (swelling of the testicles) in infection after puberty. Usually in only 1 testicle so infertility is rare. Virus can be isolated from throat washing, urine, or spinal fluid Positive mumps IgM antibody test can confirm infection, but only if patient not previously vaccinated Vaccine recommended |
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Rubella
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Similar to paramyxoviruses such as Mumps, but is a Togavirus
Transmission through resp. droplets Replicates locally and spreads through blood Humans are only source of infection Long incubation period Subtle rash that starts on face and rapidly spreads to trunk (can be pruritic in adults) Enanthem - pinpoint red macules on soft palate Forchheimer spots also suggestive of Rubella Can lead to Arthritis and thrombocytopenia Fetal infections resulting in misscariage and congenital rubella syndrome was driving force for vaccine Congenital rubella syndrome - Opthalmologic, cardiac, auditory hearing loss (common), and neurologic problems Detection of rubella-specific IgM or significant increase in rubella IgG antibody Treatment is supportive only |
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General features of Reoviridae
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Rotavirus, Orbivirus, Coltivirus, Reovirus
naked (non-enveloped) nearly spherical icosohedrons Resistant to ether and stable over large pH range to survive in stomach dsRNA |
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Rotavirus
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single most important agent of severe diarrheal illness of infants and young children
Secretes NSP4 toxin, which causes diarrhea Reoviridae family - unique b/c they are the only viruses w/ ds RNA Distinctive double-layered icosahedral protein capsid Wheel like appearance on EM RNA-dependent RNA polymerase needed for transcription of viral dsRNA into mRNA (mRNA transcribed from minus strand of dsRNA in intact core and extruded out for translation) 6 groups - Group A causes human disease VP6 - contained on inner capsid and makes up bulk of virion VP4 and VP7 - located on outer capsid and stimulate neutralizing antibodies (determine serotype) VP4 is a viral-attachment protein VP7 is a glycoprotein 1st infection as infant is often the most severe No WBC or RBC in stool shortening and atrophy of villi in small intestine and mononuclear infiltrates of lamina propria (increased by malnutrition) fecal/oral route of transmission peaks of infection move sequentially from west to east throughout the year ELISA and latex agglutination to detect group A antigen Fluids for treatment and vaccines do exist |
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Coltivirus
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Distinguished from other reoviruses b/c of its transmission via arthropod vectors (Wood tick)
Causes Colorado Tick Fever - biphasic fever, ocular pain, chills No Rash Virus infects erythroid cells and can persist Leukopenia (low WBC) is a consistent finding self-limiting so treatment is supportive Can sometimes cause Encephalitis |
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Norovirus
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Major cause of epidemic gastroenteritis of children and families
Caliciviridae family Non-enveloped, positive sense ssRNA Fastidious and lack distinctive morphology by EM diarrhea and vomiting accompanied by fever, headache, abdominal cramps Primarily disease of school-age children and adult contacts Oral/fecal transmission Short incubation The cause of many cruise ship problems - common in close populations and can come from contaminated food / water No good tests and indistinguishable from other viral causes of gastroenteritis |
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Astroviruses
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characteristic 5 or 6 point star-like appearance on EM
Not as fastidious as other Gastroenteric viruses Multiple serotypes identified nausea, vomiting, diarrhea - self limiting fecal/oral transmission 2nd most common cause of diarrhea by a virus in children, but don't end up in the hospital Treatment is supportive |
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Enteric adenoviruses
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Serotypes 40 & 41 associated w/ gastroenteritis
dsDNA virus watery diarrhea w/ fever and emesis Fecal/oral and possible fomite transmission 2nd most common cause of HOSPITAL-BASED pediatric gastroenteritis Detection assay for serotypes 40 & 41 available Treatment is supportive |
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Dependoviruses
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AKA adeno-associated viruses (AAV)
Unique b/c they require co-infection w/ helper virus such as adenovirus or herpes virus for infection No clinical symptoms or illness AAV can get integrated into chromosome 19 and then "rescued" later by helper virus Potential agent for getting genes in during gene therapy |
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Parvovirus B19
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Erythrovirus genera of Parvovirinae
nonenveloped, ssDNA virus (* Parvoviruses are the only viruses w/ ssDNA) very heat stable and H resistant (can survive stomach acid) Requires mitotically active cell in S phase for replication Only attacks erythroid precursor cells Lytic infection so lysis these cells and releases virions - leads to an arrest of RBC production and an acute decline in serum hemoglobin Can Cause: 1.)Erythema infectiosum AKA "Fifth Disease" - benign rash that spares palms and soles (MOST COMMON Manifestation) 2.)Transient aplastic crisis (TAC) - patients w/ chronic hemolysis (no rash) 3.)Arthropathy - affects peripheral joints temporarily 4.)Chronic anemia in immuno compromised patients Most common in school-aged children (school outbreaks) Transmission by resp. droplets or blood Patients w/ EI (Fifth's Disease) are infectious BEFORE rash recognized, but not after it's there Detection by B19-specific IgM or 4-fold rise in IgG antibody Immunocompromised w/ anemia won't make antibodies so need to use PCR Infusion of immunoglobulin or RBC transfusion can help |
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Alphaherpesvirinae
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Hepresviridae subfamily
HSV-1, HSV-2, VZV Rapid growth Characteristic Latency established in sensory ganglia cause cells to become multinucleated giant syncytial cells w/ intranuclear inclusion bodies This causes cell destruction, the separation of epithelium and blister formation |
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Betaherpesvirinae
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Herpesviridae subfamily
CMV, HSV-6, HSV-7 Slow infection, long replication cycle Form enlarged (cytomegalic) cells Latency in lymph, kidneys |
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Gammaherpesvirinae
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Herpesviridae subfamily
EBV, HHV-8 Limited to growth in lymphoblastoid cells only Latency established in B or T cells so associated w/ immune problems |
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General Herpesvirus characteristics
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5 types of glycoprotein spikes for immune evasions and targeting
Linear dsDNA, but unique genome (short unique sequences & long unique sequences that can form circles associated w/ tumors Enveloped so susceptible to soap, ether, heat (must be transmitted by intimate contact) Virion also contains cellular proteins that cause autoimmune response rashes Amorphous proteinaceous tegument - surrounds the dsDNA genome and acts like glue to hold envelope close to the capsid Thymidine kinase and Ribonucleotide reductase required to replicate the viral genome and TARGETED for therapy |
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Herpes virus infection of cells
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1.) Attach to cells of epidermis or dermis
2.) Entry through multiple cell-surface receptors located on surface of the virion (use your own receptors - molecular mimickry) Bind to HVEM on lymphoid cells or Nectin 1 or Nectin 2 that account for broad Herpes targets on skin, brain, spinal ganglia, etc. 3.) Upon entry, virus can either go to productive lytic infection or latent infection 4.) Productive, lytic infection - uncoating, transcription by cell's DNA dependent RNA polymerase, translation Transcription divided into 3 parts: a.) Early (Alpha) - Shuts down cell's abilities and goes back to nucleus b.) Intermediate (Beta) - DNA Polymerase involved in genome replication c.) Late (Gamma) - Glycoproteins & capsid proteins made. Assembly of virus factories and 1st sign of disease 5.) Latent infection - HSV-1 & HSV-2 travel retrograde to establish life-long latency in sensory neurons. Only LATS, which help w/ reactivation are made. Once reactivated, anterograde transport down neuron and establishes lytic cycle at surface of skin (Shingles from VZV reactivation) |
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HSV-1
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Reactivation most frequently above the waist in trigeminal ganglion
Cold sores, herpes keratitis of the eye (leading cause of blindness), swollen gums, Herpes gladitorium (from wrestling) HSV-1 is the most common cause of viral encephalitis in the US (one of few treatable causes of this) |
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HSV-2
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Reactivation below the waist in lumbar sacral ganglion
Causes most genital herpes Can shed virus during asymptomatic periods (most go undiagnosed) Treat w/ valacyclovir Pregnant women w/ HSV-2 should deliver by caesarean section Treated w/ acyclovir, which acts as a chain terminator by affecting thymidine kinase |
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Varicella-Zoster (VZV)
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Causes chickenpox & shingles
The only herpesvirus that spread person to person by coughing or sneezing Chicken pox - infect resp. tract, get into blood, and target RES. Itchy rash, fever. Can lead to pneumonia Shingles - VZV reactivates. More common and severe in immunocompromised. Severe pain, numbness, itching Chickenpox vaccine can cause breakthrough varicella in rare cases (mild form of chickenpox) |
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Cytomegalovirus (CMV)
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Characteristic "giant cells" during infection
The Largest Herpes virus Initial infection may have cold-like symptoms or rarely cause mononucleosis (EBV more common cause of this) Seroprevalence is 50% of population infected Reactivation a few times a year, but don't cause any disease unless immunocompromised Transmission by oral, sexual, in utero, or iatrogenic (blood transfusion) bone marrow transplant patients are treated prophylactically w/ ganciclovir or monitored for viremia, antigenemia, or DNAemia and given antivirals immediately at first sign of infection Infants only receive blood that has been checked for CMV b/c they can get serious infections from CMV HIV patients can have CMV reactivation leading to retinitis (leading to blindness), GI ulcers, anemia, etc. (treat w/ gancilovir and HAART to get CD4 up) Only herpesvirus transmitted efficiently transplacentally and can lead to serious birth defects (Hearing loss and retardation) |
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HHV-6 & HHV-7
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Infect T Cells
Almost everyone has it HHV-6 causes roseola - benign syndrome in early childhood w/ high fever and severe rash |
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Epstein-Barr virus (EBV)
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Can cause Mononucleosis - fever, chills, headache, and very painful pharyngitis. Also have atypical, large lymphocytes and a heterophile antibody that agglutinates in sheep's blood for diagnosis
lytic replication in oral epithelium - then infection of B cell where it goes latent and immortalizes host cells. Reactivation is asymptomatic in those not immunocompromised Heterophile antibody - IgM marker for EBV mononucleosis by agglutination of sheep erythrocytes. IgM reactive w/ VCA is a confirmatory test. During latency, viral genome mantained in nucleus as a circular "Episome" that is not integrated into host DNA During latency replication of episome is entirely dependent on host replication factors and only requires *EBNA-1 EBNA-1 - binds to latent origin of replication (OriP) and promotes episome replication and segregation of episome into daughter cells. EBNA-1 is resistant to proteases so Ebstein-Barr does not readily express MHC Class 1. This makes the virus somewhat immune to the immune system and has implications for it's ability to cause Burkitt's Lymphoma EBV may lead to certain cancers like African Burkitt's lymphoma and types of Hodgkin's lymphoma AIDs patients can develop oral hairy leukoplaia or B cell lymphomas |
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Kaposi's Sarcoma-associated herpesvirus (KSHV)
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Kaposi's Sarcoma found mainly in AIDS patients
Affects cells lining lymph system and causes skin lesions Sexual transmission Latency vascular and lymphatic endothelial cells, unlike EBV - key to developing Kaposi's Sarcoma (or sometimes B cells) Infection is not as ubiquitous as other Herpes viruses Can cause multicentric Castleman's disease - growths on lymph tissue |
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Viral Hemorrhagic Fever (VHF)
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fever accompanied by impaired coagulation that results in bleeding under the skin, within internal organs, or from orifices
Death is thought to be from visceral organ necrosis Caused by RNA viruses Filoviridae, Bunyaviridae, Arenaviridae, and Flaviviridae All Viruses that cause Hemmorhagic Fever are ENVELOPED (destroyed by ether, etc.) |
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Ebola
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Filovirus
Abrupt onset w/ rash, red eyes, headache, sore throate Can cause Ebola Hemorrhagic Fever |
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Marburg virus
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Filovirus
Causes Hemorrhagic Fever Came from African green monkeys |
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Hantaviruses
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Bunyaviruses (3 negative-sense ssRNA segments)
Hemorrhagic Fever w/ Renal Syndrome (HFRA) Can cause respiratory arrest Rodents are reservoir and transmission by aresolized urine, droppings Abrupt onset of intense headache, back and abdominal pain Can later develop low blood pressure, shock, kidney failure Hantaan and Dobrava infections more severe than Seoul and Puumala Rodent control is primary prevention |
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Crimean Congo Virus
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causes Crimean-Congo hemorrhagic fever (CCHF)
Transmitted by Ixodid ticks or infected blood (slaughter house workers at risk) Abrupt headache, high fever, back pain Red eyes, a flushed face, red throat, and petechiae on the palate As virus progresses, get large areas of severe bruising, severe nosebleeds, and uncontrolled bleeding at injection sites Diagnosis by ELISA & PCR Treatment w/ ribavirin |
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Rift Valley Fever Virus
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Epizootic during years when unusually heavy rainfall and flooding causes mosquito eggs to hatch
Mosquitos born w/ RVF and transfer infection to livestock. Humans get it from mosquito bites or body fluids of infected animals No symptoms or mild symptoms w/ fever and liver problems Some develop hemorrhagic fever or encephalitis Can cause blindness from retinitis |
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Lassa Fever Virus
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Arenavirus in Africa
Only transmitted by special species of rat so endemic to certain region only Most infections mild, but the rest have severe multisystem disease Gradual onset w/ persistent fever In severe cases can get hemorrhage, seizures, encephalopathy, bleeding from nose and mouth, renal failure IgM antibody detection or viral antigen dectection by ELISA / PCR |
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Adenoviruses
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Family of viruses
Non-enveloped w/ icosahedral capsid Linear, dsDNA Many serotypes so hard to make vaccine Respiratory illness in children and crowded areas Transmission via close contact or fecal/oral Infections usually self-limiting No vaccine in use |
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Human Papillomavirus (HPV)
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Penetrates skin through abrasion and infects keratinocyte stem cells where viral genome is maintained as stable circular episome
Latent cells accumulate to form warts As outer skin cells are lost, they are replaced by latently infected cells that differentiate inducing expression of factors that complete viral recplication and release infectious particles As a result, expression of viral antigens is restricted to cells near the surface, which are not subject to effective immune surveilance skin warts - Caused by HPV type 2 or 4 (raised) Butcher's warts - HPV 7 (in meat handlers) Plane warts - HPV 3 & 10 (FLAT, smooth, common in children) Plantar warts - HPV 1 (painful and deep on soles of feet) Oral infections - HPV 13 & 32 (focal epithelial hyperplasia), HPV 2 (common warts on lips) Genital warts - HPV 6 & 11 (benign), HPV 16 & 18 (cancerous) |
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Difference b/w Condyloma acuminatum and Condyloma planum
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Condyloma acuminatum are soft, raised papillomas found on vulva, penis, or anus. Are NOT cancerous
Condyloma planum are flat papillomas found on the cervix. ARE Cancerous |
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Transmission and Treatment of warts
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Scratching may cause subsequent spread.
Plantar warts from wet floor like public swimming pools Genital warts spread by sexual intercourse Skin wart removed by cryotherapy, laryngeal by laser, external genital by cryotherapy, or laser, cervical by laser or diathermy (high heat) Invasive carcinoma requires surgery |
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Polyoma virus
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POlyoma and PApilloma virus are part of the PA-POviridae family
small nonenveloped w/ icosahedral capsids and circular dsDNA (similar to papilloma viruses) Acquired during childhood and cause respiratory disease JC Virus - brain infection in immunocompromised called Progressive Multifocal Leukoencephalopathy AKA PML(fatal) BK virus - Affects kidneys in immunocompromised Merkel cell polyoma virus (MCV) - causes rare form of skin cancer (Mercel cell carcinoma) |
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Smallpox
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Poxviridae family (only DNA viruses that don't replicate in nucleus, but instead in the cytoplasm. The most complex structure of all known viruses)
First vaccine and first virus to be eradicated Highly contageous via aerosilized resp. secretions Flu-like symptoms, but then rash develops w/ flat red lesions that fill w/ pus and crust over (can lead to spread) Smallpox lesions develop all at once, while chickenpox lesions develop in waves Monkey pox - related virus that causes milder disease. Initially thought to be cow pox |
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Molluseum Contagiosum Virus
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Firm papules and nodules w/ central depressions
Core may produce white, cheesy material Excellent prognosis Often seen in AIDS patients |
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2 patterns of arbovirus transmission
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1.) Humans can be an incidental host - become ill, but don't develop enough viremia to infect new vector (most common). Humans usually only affected if they encroach on natural area
2.) Humans can be primary vertebrate hosts - requires high level of viremia in human host. Infected human bitten and virus transmitted to uninfected human (human-vector-human) |
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Eastern Equine Encephalitis
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RNA virus in Togaviridae family
Mosquito transmission to humans Most severe and potentially fatal of the arboviral encephalitides |
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Arboviral Encephalitis
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1.) Eastern Equine Encephalitis - most severe. Frequent neurologic problems in survivors. Complete recovery uncommon
2.) Western Equine - mosquito transmitted, epizootic outbreaks in horses may precede human outbreaks (RNA Togaviridae virus). Outcome generally good, worst in elderly. West of the Mississippi 3.) St. Louis Encephalitis - Highest in gulf states. Mosquito transmission. Epidemics in urban and suburban areas near ground water. Close to human habitation. Usually complete recovery 4.) La Crosse / California - RNA virus in Bunyaviridae family. Tree breeding mosquitoes. Endemic in Eastern US. Disease in school-aged. Recovery usually complete 5.) West Nile Encephalitis - throughout all of US. Flaviviridae family. Mosquito transmission. Affects wide variety of birds. Disease in old. Risk of meningitis and flaccid paralysis that increases w/ age. 6.) Colorado Tick Fever - Reoviridae family. Tick transmission. More common in elevation areas. Ingestion of raw milk can also lead to infection. Vaccine available. 7.) Powassan Virus - Flaviviridae family. Tick vector. Rare cause of encephalitis, but w/ high incidence of neurologic problems. Early symptoms - fever, headache, anorexia Progression to encephalitis - altered mental status, photophobia, severe headache Diagnosed by travel history and Detection of IgM antibody or four fold increase in IgG antibody Treatment is intensive supportive care |
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Japanese Encephalitis Virus
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Most important global cause of arboviral encephalitis
RNA Flaviviridae virus Mosquito vector that feeds at night More severe disease in children Can cause acute flaccid paralysis that rarely recovers Treatment is supportive Vaccine is used internationally and recommended for travelers |
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Murray Valley Encephalitis
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Uncommon, but high mortality
RNA Flaviviridae virus Mosquito vector Half of survivors have problems Children and elderly at highest risk No vaccine |
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Dengue fever
Dengue hemorrhagic fever |
Dengue fever - benign syndrome characterized by biphasic fever, severe back pain ("back-break fever")
Dengue hemorrhagic fever - often fatal disease w/ increased capillary permeability, protein-losing shock syndrome called Dengue Hemorrhagic Shock Syndrome. Appears to occur mainly in people who have had previous dengue infection The most important arthropod transmitted viruses Treatment is intensive care supportive and Aspirin should be avoided |
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Dengue Viruses
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RNA Flaviviridae family
Can cause Dengue fever (break-back fever) or Dengue Hemorrhagic Fever, which is life threatening Maintained through a human-mosquito-human cycle (humans are primary host) Daytime feeders that prefer to bite humans and breed in or close to houses (short flight distance so stay close to humans) Spread of epidemics follows main major roadways |
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Yellow Fever
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Viral hemorrhagic fever characterized by hepatic, renal, and myocardial injury
High fatality ratio In South American and Africa Prototype of Flaviviridae family (enveloped, ssRNA Virus) Transmission cycle w/ monkeys and daytime biting mosquitoes "Jungle yellow fever" - monkey to vector to monkey "Urban yellow fever" - human to vector to human Wide range of outcomes - subclinical infection, nonspecific febrile illness, Life-threatening disease w/ fever, jaundice, and renal failure 3 stages: 1.) Period of infection - Viremia present, sudden onset of symptoms, flushing of face and neck 2.) Period of remission - fever and symptoms resolve for 48 hours. Most patients recover here 3.)Period of intoxication - Viremia resolves and ANTIBODIES APPEAR. Return of fever, w/ jaundice, renal dysfunction, and hemorrhage Treatment is supportive: maintain nutrition, FFP for bleeding, dialysis, treatment of secondary infections Live, attenuated vaccine available |
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Encephalitis
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Inflammation of brain
Hallmark is altered consciousness Fever, headache Hemi paresis, seizures, reflex abnormalities Viruses are the most common cause |
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Meningitis
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Inflammation of leptomeninges (coating of the brain)
Headache, stiff neck (Focal neurological findings usually absent) Aseptic meningitis - usually viral. Mononuclear cells (lymphocytes), near normal Glc and proteins in CSF. Septic meningitis - Usually bacterial. Low Glc, high protein in CSF. |
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Myelitis
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Inflammation of spinal cord
limb weakness, Ascending flaccid paralysis Poliomyelitis like syndrome involving anterior horn w/ flaccid paralysis and NO sensory loss |
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Viruses that cause CNS problems (Lots of them)
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1.) Herpesviridae - Most common virus to cause encephalitis. Temporal / frontal lobe necrotizing infection (very destructive unlike other viral forms). CSF PCR is gold standard for diagnosis. Treat w/ IV Acyclovire. (Most Common Encephalitis in the winter)
2.) Enterovirus - Most common virus for Meningitis (Coxackie group B and echovirus). High during summer. Children commonly. Paralytic disease of ascending flaccid paralysis may result. Use PCR to diagnose. 3.)Epstein-Barr - Aseptic meningitis commonly seen w/ mononucleosis. Encephalitis, myelitis can be seen. Elevated transamminases, atypical lymphocytosis in CSF and SPLENOMEGALLY can be used to diagnose 4.) Human Herpes Virus 6 - quite neurotropic, causes menigoencephalitis. Persists indefinitely and may cause chronic CNS problems. 5.) Rhabdoviridae - silver haired bat MCC of rabies in US. "Furious form" - agitation, delirium, hydrophobia, myocarditis - death from myocarditis Paralytic "dumb" form - Ascending flaccid paralysis, coma follows Diagnose w/ Fluorescent antibody of "nape" of neck Rabies immnoglobulin and rabies vaccine for unvaccinated patient. 6.) Lymphocytic Choriomeningitis Virus (LCM) - common in DC in Fall / winter. Mouse transmission. Fever and rash improves, then recurs w/ meningitis. May cause orchitis (inflammation of testicles) or myocarditis. CSF w/ increased pressure and proteins. 7.) Paramyxaviridae - May cause encephalitis. Recipients of vaccine or immunocompromised may get encephalitis 8.) Varicella-Zoster - Aseptic meningitis common w/ chicken pox and self-limited. Encephalitis, Bell's palsy 9.) Adenovirus - Serotype 7 occasionally cause meningitis or encephalitis. Chronic form occurs w/ hypogammaglobulinemia (like w/ enterovirus) Ribavirin to treat 10.) HIV - Meningitis, encephalitis, Bell's Palsy since HIV infects brain. Can lead to dementia. Deep grey & white matter microglial cells infected, neurons are not. |
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Arthropod Viruses that cause CNS problems
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ELISA test to detect all
Transmission by mosquito, except Tick born Encephalitis 1.) LaCrosse virus - Mild meningitis to severe HSV-like illness. Mostly in young. 50% w/ seizures. East of Mississippi 2.)Eastern Equine Encephalitis - Severe disease w/ basal ganglia and brainstem abnormalities on MRI 3.) St. Louis Encephalitis virus - Used to be significant cause of encephalitis. Similar, but milder to EEE. Flaviviridae 4.) West Nile Virus - Ascending flaccid paralysis is a unique feature. Spread quickly via migrating birds 5.) Japanese Encephalitis Virus - Big problem globally. Primarily in children. 1/3 of patients have CNS palsy's and muscle weakness. Pakistan to Russia. Vaccine available 6.) Tick Born Encephalitis - similar to JEE and causes paralysis and palsy |
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HIV general characteristics
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Lentiviridae family (long incubation period and progressive disease despite immune system)
HIV-1 and HIV-2 HIV-1 the one in US and acts more quickly HIV-2 in Africa and slower onset to AIDS Globally, heterosexual transmission is the most common Infects CD4+ T cells, macrophages, and glial cells Genome made up of: LTR on both ends (form sticky ends of integration and have promoter activating functions) gag - codes for all of the viral core proteins pol - codes for viral protease, integrase, and reverse transcriptase (protease needed as post-translational modification to cleave gag and pol out) env - form envelope proteins - gp120 & gp41 |
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HIV Entry into cell
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Binds to CCR5 and CXCR4 on CD4+ T cells
HIV gp120 binds to CD4+ and get conformational change so it can then bind CCR5 or CXCR4 HIV gp140 is then rammed into the CD4+ cell and causes fusion of HIV and the cell so that internalization can occur A single HIV virion causes initial disease so stopping this initial binding is a good site for therapy (important to give anti-retrovirals early) |
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Host mechanisms that try to resist HIV infection
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APOBEC is host defense mechanism that deaminate cytidines in retroviral DNA, but HIV makdes Vif that deactivates APOBEC
TRIM5 - targets incoming retroviral capsids and accelerates their disassembly |
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HIV-1 Reverse Transcription & Integration
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Virus must first uncoat once it's in the cell
Reverse transcription carried out by reverse transcriptase - results in double stranded Viral DNA from ss RNA of HIV and Long Terminal Repeats on both ends of the genome *Reverse Transcriptase lacks ability to edit so you get lots of mutations - makes HIV very adaptable and resistant to anti-virals HIV uses Vpr to move into nucleus and Integrase cuts host genome, modifies LTR repeats on HIV and attaches it to the host genome (now a provirus) Provirus can't be touched by anti-retrovirals b/c uses host machinery to replicate |
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RT-PCR for HIV
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Uses reverse transcriptase to turn viral RNA into DNA that is then amplified
Look at this DNA to determine viral load (does not measure latent virus or provirus) or to determine if there are any mutations that might make the virus resistant to anti-retrovirals Viral loads correlate w/ disease progression Goal is to get Viral load to undetectable amounts, but virus is STILL THERE ELISA & Western Blot combo used to test for HIV (now using saliva testing) Don't have to get explicit consent to do testing, just tell patient you're doing it and they can opt out If patient has been off meds for a while, resistance testing won't help b/c non-resistant WT strain is more fit and will be the most prevalent |
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HIV Latency, Reactivation, and Transcription
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Latency can occur for a period of time and can stop when antivirals are stopped
infection or other insult leads to increased NF-kb - this leads to increased transcription and reactivation Tat and Rev regulate transcription: Tat allows host cell RNA polymerase to make full length HIV RNA w/out aborting prematurely Rev binds HIV RNAs and moves them out of the nucleus for translation and BYPASSES Splicing - this "REVs up the reading of gag, pol,, and env to produce virions |
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HIV Assembly and Transmission
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Nef and Vpu strips CD4 and MHC Class 1 off of HIV infected cells - allows HIV to get to lipid rafts to pick up proteins and bud off
Viral protease in immature HIV cleaves HIV so it can turn into mature virion (some drugs stop this - virus can enter cell, but can't replicate) Transmitted sexually, in breast milk, perinataly, and in very rare cases orally Perinatal transmission has greatly decreased since the introduction of AZT given to pregnant women STDs increase risk of getting HIV Deletion of CCR5 in rare individuals can make them immune from infection Transmission from needle stick is the greatest w/ large, hollow needle that punctures deep (post-exposure prophylaxis greatly decreases risk) |
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HIV Pathogenesis
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Intially may get flu-like symptoms that resolves (No antibodies measured at this time, but DO have very high Viral loads that can be measured*)
Also get significant destruction of GALT early on Viral load is highest during acute infection so highest possibility of transmission Over following years, patient may be asymptomatic, but immune system aging quickly and CD4 levels dropping. *Oral Hairy Leukoplakia, mucosal candidiasis, shingles, and ulcers from HSV may be seen. Elevated IL-6, D-dimer, and C-reactive protein causes "inflamm-aging" Virus collected by dendrites & taken through lymph nodes - replicate in CD4+ cells and then goes to other organs HIV replicates very rapidly In antiviral era, many die from malignancy, heart disease, renal disease |
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Diseases seen w/ certain CD4 T cell counts in HIV patients
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CD4>500 - Candida vaginitis
CD4 200-500 - Pneumococcal pneumonia, Pulmonary TB, Shingles, Oral Hairy Leukoplakia, Kaposi's sarcoma CD4<200 - Pneumocystis jiroveci pneumonia (PCP - Most common opportunistic infection and prevented w/ bactrin), extrapulmonary TB CD4<100 - Toxoplasmosis (reactivation that causes brain abscesses, give bactrin to prevent) CD4<50 - CMV (Can cause retinitis so get eye exam), MAC (opportunistic, causes wasting disease, treat w/ Azithromycin) HIV associated w/ neoplasms - Kaposi's sarcoma from HHV-8, Non Hodgkins B cell lymphoma from Epstein Barr, Cervical carcinoma from HPV |
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Highly Active Antiretroviral Therapy (HAART)
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combo therapy w/ 3 or more antiretrovirals for HIV
Works well when meds are adhered to Rapid rebound of virus if HAART stopped Nonadherance breeds resistance |
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Immune Reconstitution Syndrome (IRS)
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Due to rapid restoration of pathogen-specific immunity w/ suppression of HIV
Patients w/ advanced disease at the time HAART is initiated may initially develop worse disease Treatment is to treat underlying opportunistic infection and continue HAART |
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Prions
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small proteinaceous infectious particles that are resistant to deactivation and cause aggregates to form in the brain - fatal
Prions transform normal prion protein w/ an alpha structure (PrPC) to abnormal proteins w/ a Beta structure that cause aggregates to form (PrPSc) Aggregates destroy nerve cells and form sponge-like holes in the brain Transmissible from animal to animal Lack antigenicity or immunogenicity Produce encephalopathy and not encephalitis Long incubation periods Cause disease, but genetic determinants are a factor Spongiform diseases can also occur spontaneously without known infectious process Can cross species |
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Kuru
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Fatal prion disease found only in the Fore tribe in New Guinea
Comes from ingestion of brain tissue from those that had died of the disease Clinically resembles CJD Grossly, congestion of blood vessels and cortical atrophy Microscopically, spongy appearance and brush like plaques called "spike balls" found in cerebellum |
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Alzheimer's Disease
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Progressive form of dementia that affects amygdala and hippocampus
Caused by amyloid plaques and intracellular accumulations of tau protein |
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Jakob-Creutzfeld disease (CJD)
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Prion disease that causes loss of motor control, dementia, paralysis and eventually death following pneumonia
Cerebral involvement and patient rarely survives a year Cortical atrophy seen grossly Cannot distinguish b/w this and Kuru (look the same macroscopically as well) Need PRNP to develop this disease Familial and Sporadic |
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Gerstman-Strausser Schinker Disease (GSS)
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Occurs in 4th -5th decade
Prion disease w/ cerebellar ataxia and motor problems Dementia less common and lasts several years until death (Different from CJD) Familial and Sporadic |
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Bovine Spongiform Encephalopathy (BSE)
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AKA Mad Cow disease
reached epidemic proportions in UK Associated w/ CJD in young caused by mutant BSE Scrapie to Mad Cow to CJD in young Can't be distinguished from CJD or Kuru Chronic Wasting Disease is the cousin of mad cow found in deer in the USA |
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2 ways that humans are infected by prions
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1.) Acquired infection - ingestion and prion is taken up by MALT, to Preyer's Patches, to Lymph, then enters CNS
1.) Apparent hereditary Mendelian transmission - Autosomal dominant and no infectious agent present prions are both infectious AND hereditary |
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Difference b/w Normal, Immortalized, and Transformed cells
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normal cells require specific growth factors, attachment to a substrate, are contact inhibited, and will undergo only a limited # of replications
Immortalized cells - will undergo unlimited cell divisions in culture Transformed cells - immortal, may grow unattached, no longer require growth factors, or are not contact inhibited (often tumor cells) |
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Direct Oncogenic Mechanisms of Oncogenic RNA Viruses (retroviruses)
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retroviruses have LTRs on both ends - 5' end LTR = promoter, 3' end LTR = polyadenylation site
Acutely Transforming retroviruses - Most have lost essential viral genes to make room for oncogenes so they are defective viruses and need helper virus to work. Integrate into host genome and 100% effective at transforming cells regardless of where it integrates. Work by constantly turning on signal transduction pathways Rous sarcoma is the only acute transforming virus that is non-defective and has the full RNA genome needed to replicate and also causes tumors Chronic transforming retroviruses - Don't contain oncogenes so don't transform cells in culture, but can replicate autonomously. Has to randomly integrate into an area near a proto-oncogene to form tumor (takes a long time). Can occur by: 1.) Viral promoter activation (right beside the promoter) 2.) Viral enhancer activation (cluster near proto-oncogenes No retroviral oncogenic virus in humans |
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Direct Oncogenic Mechanisms of concogenic DNA viruses
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Unphosphorylated pRB usually binds E2F and prevents transcription
E7 from Papilloma virus binds up PRB & leads to lots of transcription Normally, DNA Damage or the presence of a virus induces p53, which blocks p21 and transcription stops E6 from Papilloma virus degrades p53 and E1B binds up p53, which leads to inability to turn off transcription and elevated transcrpition HPV 16 & 18 are the cancerous serotypes and are targeted by Merck GARDASIL vaccine |
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Polyomavirus causes of cancer
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previously, many people received vaccine that had SV40 virus in it, which has been shown to be cancerous
SV40 inactivates both pRB and p53 Merkel cell polyomavirus can cause Merkel cell carcinoma (rare skin cancer) |
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Indirect Oncogenic Mechanisms of Oncogenic DNA and RNA viruses
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Slow process. Often need other mutations
Examples - EBV and Burkitt's lymphoma - infects B cells and establishes latency there. During latency only EBNA-1 expressed. Also contain translocation that dysregulates c-myc. Since EBNA-1 peptides are not attacked by the immune system, they can grow into lymphomas EBV only indirectly contributes to lymphoma by providing a pool of rapidly dividing, immortalized B-cells, thereby increasing odds that mutations in genes necessary for lymphoma will occur Kaposi's sarcoma associated w/ herpesvirus - similar mechanism to EBV, but act on endothelial cells rather than B-cells HTLV-1 causes T-cell cancer - May act through Tax, which produces IL-2 that can chronically increase T cell production. Tax also inhibits p53 Hepatitis B & C - Damage liver - lots of cell proliferation to heal - can lead to carcinoma b/c of accumulations of mutations |
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General characteristics of vaccines
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Developed to present antigens to host in a controlled fashion for immunity production
Antigens can be protein, polysaccharide, conjugate, whole killed / attenuated viruses, or subunits Effective schedule of vaccines must be determined Valency - How many things you immunize against w/ single vaccine Can use antibody testing for assessment of vaccine receipt or measurement of efficacy (Screen healthcare workers for Hep B antibodies for protection) Can also use tetanus titer to figure out where immune system is deficient |
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Toxoid vaccines
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Tetanus, Diptheria, Pertusis
Antibodies that destroy toxin T-cell Dependent Primary series in infancy w/ boosters as adults Generally given in combo vaccines (Tdap, Td, etc.) |
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Killed / Inactivated vaccines
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Hep A, Polio, Influenza
Can be given to immunocompromised T-cell dependent Primary series in infancy Inactivated version of Polio vaccine won't cause vaccine-aquired paralytic polio |
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Polysaccharide vaccines
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Pneumococcal invasive disease, meningococcal disease, typhoid fever
T-cell INDEPENDENT (Don't initiate T cell memory, DO NOT use in children) Given to at risk patients w/ subsequent doses as needed Inconsistent response and idiosyncratic response to subsequent doses so next dose can cause less response (especially in meningococcal vaccine) |
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Conjugate Vaccines
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Haemophilus influenzae meningitis, invasive pneumococcal disease, meningococcal disease
Conjugated to a protein T-cell dependent Primary series (Hib) or single dose w/ boosting Pneumococcal conjugate vaccine can have cross-strain protection and some elimination of pathogen from nasopharynx |
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List the DNA Viruses
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HHAPPPy viruses:
Herpes Hepadna Adeno Papova Parvo Pox Parvoviridae is the only ssDNA virus (One PAR golf is simple) Poxviridae is complex and is the only DNA virus that replicates in the cytoplasm 3 DNA Viruses are naked - A woman must be naked for the PAP smear: PApova, Adeno, PArvo |
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(+) Stranded RNA Virus Families
(-) Stranded RNA Virus Families |
(+) Stranded -
"The CALCIfied old Emperor PICO is wearing his Crown and TOGA and is eating FLAVorful grapes from a RETRO bowl Calici, Pico, Corona, Toga, Flavi, and Retroviridae (-) Stranded - "Old Pete's RABid dog FILO fights Paul BUNYon in the ARENA" Orthomyxo, Paramyxo, Rhabdo, Filo, Buny, and Arenaviridae |
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Differences b/w chicken pox lesions and smallpox lesions
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Chicken pox = superficial lesions
Smallpox = deep, hard lesions C= lesions not umbilicated S = Lesions umbilicated w/ central depression C = Lesions on the trunk S = Lesions on extremities |
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Diseases that can be passed to unborn fetus
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TORCHES
TOxoplasmosis Rubella Cytomegalovirus HErpes, HIV Syphilis |
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Types of Arboviruses
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Paul BUNYan wearing a TOGA, has a rich FLAVOr that attracts mosquitos and arthropods and cause headaches (encephalitis)
Bunyaviridae - California encephalitis, Hentavirus (respiratory failure) Togaviridae - Alpha (EEE, WEE) and rubivirus(not an arbovirus) Flaviviridae - St. Louis encephalitis, yellow fever, dengue fever, West Nile virus |
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Viruses that cause diarrhea
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"If your CALICO cat develops ASTROnomical diarrhea, ROTAte the kitty litter frequently, ADE(and) ROTATe the cat off to NORWAy"
Calciviruses including Noroviruses Rotaviruses Adenoviruses Astroviruses |
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Icosahedron capsid containing DNA and RNA viruses
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DNA:
"HAPP" - Herpetoviridae, Adenoviridae, Papovaviridae, Parvoviridae RNA: "It's a TRP!" - Togaviridae, Rheoviridae, Picornaviridae Icosahedral viruses have 5-fold, 3-fold, or 2-fold symmetry, and are made of capsomeres Poxviridae is the only "complex" virus that infects humans. Complex viruses DO NOT HAVE A CAPSID, but instead have a mixture of protein and lipid material. |
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All viruses w/ envelope have a lipid bilayer except:
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Hepadnaviridae & poxviridae
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RNA viruses w/ segmented RNA
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a BOAR has cut up the DNA
Bunyaviridae, Orthomyxoviridae, Arenaviridae, Rheoviridae |
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DNA viruses w/ circular DNA
RNA viruses w/ Circular RNA |
pH
Papovaviridae and Hepdnaviridae Ab Arenaviridae & Bunyaviridae |
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Viruses that remain localized to the respiratory tract and don't disseminate through the rest of the body
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Orthomyxoviridae, Paramyxoviridae, Coronaviridae, and Rhinoviridae
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